TY - JOUR
T1 - Antigen-specific activation and proliferation of cd4+and cd8+t lymphocytes from brucellosis patients
AU - Moreno-Lafont, Martha Cecilia
AU - López-Santiago, Rubén
AU - Zumarán-Cuéllar, Elena
AU - Paredes-Cervantes, Vladimir
AU - López-Merino, Ahidé
AU - Estrada-Aguilera, Ariel
AU - Santos-Argumedo, Leopoldo
N1 - Funding Information:
Acknowledgements This work was supported in part from a grant from Consejo National de Ciencia y Tecnologia, CONACyT, Mexico (411300-5-32678-M); from the United Nations University (Tokyo, Japan); and from Coordinacibn de Estudios de Pos-grado e Investigacibn, I.P.N., Mexico (200399 and 200390). M. C. M.-L., R. L.-S. and A. L.-M. are EDD and COFAA fellows; and L. S.-A. is an SNI fellow. The authors are grateful to S. Partida-Sbnchez for invaluable technical support and to Dr Iris Estrada-Garcia and Dr Leopold0 Flores for critical revision of the manuscript.
PY - 2002
Y1 - 2002
N2 - Salt-extractable antigen from Brucella melitensis 16M (RCM-BM) was used to evaluate the immune response from acute and chronic patients suffering from Brucella infections (in Mexico); their responses were compared with those of healthy controls. As a readout we used upregulation of CD69 (a well-established early activation marker for lymphocytes), lymphocyte proliferation by 3[H]thymidine or 5-bromo-2-deoxyuridine (BrdU) incorporation measured by liquid scintillation or flow cytometry, respectively, and production of gamma interferon (IFNγ). We compared the antigen-specific response with the response induced by phytohaemagglutinin (PHA) as a positive control. There was no difference between acute patients and the healthy controls in the percentages of CD3+, CD4+or CD8+lymphocytes. However, we found that chronic patients had a significant (P < 0.05) increase in the CD8+T cells, in line with previous studies. Antigen-specific responses to RCM-BM showed a significant (P < 0.05) upregulation of CD69 in both CD4+and CD8+T lymphocytes in acute brucellosis patients and in CD8+T lymphocytes in chronic patients, indicating that both populations became activated by this antigen preparation. Moreover, lymphocyte proliferation from both acute and chronic patients in response to RCM-BM was highly significant (P < 0.001) when compared with healthy controls. However, there were no apparent differences between acute and chronic patients. Although the incorporation of BrdU showed similar results it provided additional information, since we demonstrated that both CD4+and CD8+T lymphocytes from acute and chronic patients proliferated equally well in response to RCM-BM. Similar results were observed with intracellular IFNγ determination. As a whole, our data suggest an important role for both CD4+and CD8+T lymphocytes in Brucella infection in humans. As has been reported in mice, it is feasible that activated CD8+T participate in protection against Brucella in humans through cytotoxicity or/and by the production of factors such as interferon and granulysin. The role of these cells should be carefully analysed to understand better their participation in human infection by Brucella.
AB - Salt-extractable antigen from Brucella melitensis 16M (RCM-BM) was used to evaluate the immune response from acute and chronic patients suffering from Brucella infections (in Mexico); their responses were compared with those of healthy controls. As a readout we used upregulation of CD69 (a well-established early activation marker for lymphocytes), lymphocyte proliferation by 3[H]thymidine or 5-bromo-2-deoxyuridine (BrdU) incorporation measured by liquid scintillation or flow cytometry, respectively, and production of gamma interferon (IFNγ). We compared the antigen-specific response with the response induced by phytohaemagglutinin (PHA) as a positive control. There was no difference between acute patients and the healthy controls in the percentages of CD3+, CD4+or CD8+lymphocytes. However, we found that chronic patients had a significant (P < 0.05) increase in the CD8+T cells, in line with previous studies. Antigen-specific responses to RCM-BM showed a significant (P < 0.05) upregulation of CD69 in both CD4+and CD8+T lymphocytes in acute brucellosis patients and in CD8+T lymphocytes in chronic patients, indicating that both populations became activated by this antigen preparation. Moreover, lymphocyte proliferation from both acute and chronic patients in response to RCM-BM was highly significant (P < 0.001) when compared with healthy controls. However, there were no apparent differences between acute and chronic patients. Although the incorporation of BrdU showed similar results it provided additional information, since we demonstrated that both CD4+and CD8+T lymphocytes from acute and chronic patients proliferated equally well in response to RCM-BM. Similar results were observed with intracellular IFNγ determination. As a whole, our data suggest an important role for both CD4+and CD8+T lymphocytes in Brucella infection in humans. As has been reported in mice, it is feasible that activated CD8+T participate in protection against Brucella in humans through cytotoxicity or/and by the production of factors such as interferon and granulysin. The role of these cells should be carefully analysed to understand better their participation in human infection by Brucella.
KW - Antigens
KW - Brucella melitensis
KW - Brucellosis
KW - CD4T cells
KW - CD69T cells
KW - CD8T cells
KW - Immune response
KW - Lymphocyte proliferation
KW - Mexico
UR - http://www.scopus.com/inward/record.url?scp=0036069042&partnerID=8YFLogxK
U2 - 10.1016/S0035-9203(02)90119-7
DO - 10.1016/S0035-9203(02)90119-7
M3 - Artículo
SN - 0035-9203
VL - 96
SP - 340
EP - 347
JO - Transactions of the Royal Society of Tropical Medicine and Hygiene
JF - Transactions of the Royal Society of Tropical Medicine and Hygiene
IS - 3
ER -