Ratios of effector to central memory antigen-specific CD4(+) T cells vary with antigen exposure in HIV+ patients.
The OX40/CD25 assay is a novel technique that assesses antigen-specific CD4(+) T-cell responses. To unequivocally demonstrate that responding cells are memory cells that become activated after secondary stimulation, naïve CD45RA(+) and memory CD45RO(+) populations were stimulated with cytomegalovirus (CMV) lysate and the combined expression of CD25 and OX40 measured. As expected, the naïve population showed very little response, whereas there was a higher response from the memory counterpart. To further elucidate CD4(+) memory T-cell subsets involved in recall responses, CD4(+) T cells were separated into central memory (Tcm) and effector memory (Tem) subsets and stimulated with antigen-pulsed antigen-presenting cells (APCs). CMV responses in healthy donors showed a Tem-dominant response with a Tem/Tcm ratio of 1.2, whereas the tetanus toxoid responses were dominated by a Tcm response with a Tem/Tcm ratio of 0.35. To determine memory response in the chronic of HIV infection, patient samples were used. A similar pattern to healthy donors was observed in seven chronic HIV+ patients at week 4 after anti-retroviral therapy who responded to CMV with a larger response coming from Tem. The pattern was similar after 48 weeks of therapy but the responses were lower in magnitude. In chronic HIV+ patients who respond to Gag peptides, following institution of therapy there was an inversion of the ratio of the responding memory subsets compared with week 4, with a greater response from Tcm at week 48. This result was concordant with reduction in antigen load. As immune activation decreased there was also a decrease in the percentage of responding effector memory cells and maintenance of long-term central memory.
1] Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia [2] Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia.
Chansavath
C
Phetsouphanh
1] Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia [2] Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia.
Yin
Y
Xu
1] Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia [2] Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia.
Michelle
M
Bailey
Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia.
Sarah
S
Pett
1] Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia [2] Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia.
John
J
Zaunders
Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Nabila
N
Seddiki
1] Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia [2] Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia.
Anthony D
AD
Kelleher
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D018655:Lymphocyte Count; D053262:Receptors, OX40 / Q000378:metabolism
D015488:HIV Antigens; D053262:Receptors, OX40