I believe that the mature T lymphocytes may be out in various tissues in the lymphatic system. I had occasionally wondered about this myself, since back in grad school I learned that the thymus is replaced by connective tissue after puberty. However, after more research, I think the truth is that while the active tissue in the thymus shrinks as we age, the loss of the epithelium (where most of the action is) happens so slowly that few people live long enough to completely outlast it. Of course, we do get decreased immune function with age.

This makes evolutionary sense. We get fewer new T-cells and lessdifferentiation of cells as we age, but it's less important then. After all, we are born with all of the variety of T-cells we'll ever have. Exposure just allows us to make active and memory cells for each clone. Back when we lived in small groups, rarely went very far, and rarely contacted anything or anyone from very far away, how many new pathogens were we going to see after age 15? Thymus tissue may be expensive to support, so why keep it after you had produced your lifelong arsenal? Besides, people were probably lucky to live to age 40.

Now that we may live to past 90 and spend our lives jetting around the globe and eating food grow on another continent, it would be great to still have an active thymus, but that's a problem with evolution, it can't look ahead to see what you'll need in the future.

As you may know, T-cell progenitor cells (stem cells) originating in bone marrow migrate to the thymus where they undergo a remarkable maturation process.Here, the immature T-cells (thymocytes) differentiate into different classes, including T-helper cells and cytotoxic T-cells. Afterwards, the cells undergo a critical selection process in which only T-cells capable of recognizing non-self antigens displayed on the surface of "professional" antigen-presenting cells (e.g. macrophages, dendritic cells) are allowed to survive. As much as 98% of the T-cells fail this selection process and are degraded. The rest migrate to peripheral sites throughout the body to perform their specific immunological roles. To see animation illustrating this process in more detail, go to

The immune system's library of T-cells is largely built early on in life. A stockpile of memory T-cells is created (generated by previous exposure to foreign antigens), helping to prepare your body for future infections. The thymus begins to shrink after puberty and its capacity to produce immune cells gradually reduces, but may not completely diminish. Also, while the majority of T-cells mature in the thymus, there have been reports of T-cell maturation in the liver and intestines. This means that if an older adult is exposed to a unique antigen he/she has never encountered before, a T-cell response is still possible. However, this response may not be as efficient as it would be in a child. With this in mind, it seems then that the philosophy of keeping our kids as clean and germ-free as possible may actually limit their ability to build a strong, healthy immune system!