Lack of ICAM-1 on APCs during T cell priming leads to poor generation of central memory cells.
ICAM-1/LFA-1 interactions are known to enhance T cell/APC interactions and to promote T cell activation and cytokine secretion. We have analyzed the consequences of ICAM-1-mediated signaling on the generation of memory T cell subsets. We report that lack of ICAM-1 on APCs, but not on T cells, leads to poor T cell activation and proliferation in vitro and in vivo, and that the defect can be compensated by Ag dose, exogenous IL-2, additional costimulation, and by increasing responder T cell density on APCs. ICAM-1-null mice do not respond to immunization with OVA peptide, but immunization with OVA or with Salmonella typhimurium leads to good T cell proliferation 7-10 days later, and clearance of a challenge infection is equivalent to that of wild-type mice. However, when followed over time, recall proliferation and antibacterial immunity decay rapidly in ICAM-1-null mice, while recall cytokine responses are unaffected. The decline in immunity is not related to poor survival of T cells activated on ICAM-1-null APCs, or to poor generation of effectors in ICAM-1-null mice. Phenotypic analysis of T cells stimulated on ICAM-1-null APCs reveals preferential generation of CD44(high) CD62L(low) effector memory cells (T(EM)) over CD44(high) CD62L(high) central memory cells (T(CM)). Further, while the proportion of naive:memory T cells is similar in unmanipulated wild-type and ICAM-1-null mice, there is an accumulation of T(EM) cells, and a high T(EM):T(CM) ratio in aging ICAM-1-null mice. Together, the data indicate that signaling through LFA-1 during T cell activation may be involved in commitment to a proliferation-competent memory pool.
Parameswaran
Neetha
N
National Institute of Immunology, New Delhi, India.
Suresh
Radhakrishnan
R
Bal
Vineeta
V
Rath
Satyajit
S
George
Anna
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000235:genetics*; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation
D018799:Intercellular Adhesion Molecule-1