T-cell differentiation occurs within the thymus and is characterized by ordered expression of various CD surface molecules and V, D, and J gene rearrangements. Progenitor cells originating in the bone marrow migrate to the thymus. These early pre-T cells are CD3−CD4−CD8− triple negative (TN) cells. TN cells differentiate into CD3−CD4+CD8− intrathymic T progenitor (ITTP) cells. ITTP subsequently differentiate into CD3+CD4+CD8+ double positive (DP) T cells. DP thymocytes undergo apoptosis if their TCR fails to recognize an antigen. Negative selection or apoptosis also occurs if the antigen binding avidity is too strong. Positive selection or survival appears to occur only if antigen binding is of moderate avidity. Along with positive and negative selection, DP thymocytes differentiate into single positive (SP) cells either CD3+CD4+CD8−(CD4 SP) or CD3+CD4−CD8+(CD8+ SP) and exit the thymus as recent thymic emigrants into the blood and lymphoid tissues. Via their TCRs, CD4+ SP and CD8+ SP T cells recognize peptide bound to MHC class II and I molecules, respectively.5–7
